Proteomic analysis in lung tissue of smokers and COPD patients

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Abstract

Rationale: Although cigarette smoking is the most important risk factor for COPD, COPD develops in only a minority of smokers, suggesting a significant genetic role. To solve the underlying pathophysiologic mechanism, it is critical to understand genes and their final product, ie, proteins. We investigated the exclusive proteins from the lung tissues obtained from COPD patients using proteomics. Methods: Nontumorous lung tissue specimens were obtained from patients who underwent surgery for lung cancer. We included 22 subjects: nonsmokers (n = 8), smokers without COPD (healthy smokers, n = 7), and smokers with COPD (n = 7). Proteins were separated from their spots with two-dimensional polyacrylamide gel electrophoresis and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). To validate the proteins from the above procedures, Western blotting and immunohistochemistry were conducted. Results: Twelve protein spots from COPD group significantly increased or decreased compared with the other two groups were chosen for MALDI-TOF-MS analysis. Eight proteins were up-regulated in the COPD group as compared with the nonsmokers. Meanwhile, five proteins from the COPD group were up-regulated and five were down-regulated when compared with healthy smokers. Of these, matrix metalloproteinase (MMP)-13 and thioredoxin-like 2 were significantly increased in the COPD patients by Western blot and immunohistochemistry. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes; however, thioredoxin-like 2 was primarily seen in the bronchial epithelium. Conclusions: MMP-13 and thioredoxin-like 2 in lungs increased in patients with COPD. MMP-13 was mainly expressed in the alveolar macrophages and type II pneumocytes. In contrast, thioredoxin-like 2 was primarily seen in the bronchial epithelium.

Original languageEnglish
Pages (from-to)344-352
Number of pages9
JournalChest
Volume135
Issue number2
DOIs
Publication statusPublished - 2009 Feb 1

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Keywords

  • Matrix metalloproteinase 13
  • Proteomics
  • Pulmonary disease, chronic obstructive
  • TXNL2 protein, human

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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